PLoS One [Accessed 21 March 2015]

PLoS One
[Accessed 21 March 2015]
http://www.plosone.org/

Research Article
Mechanisms of Immunity in Post-Exposure Vaccination against Ebola Virus Infection
Steven B. Bradfute, Scott M. Anthony, Kelly S. Stuthman, Natarajan Ayithan, Prafullakumar Tailor, Carl I. Shaia, Mike Bray, Keiko Ozato, Sina Bavari
Published: March 18, 2015
DOI: 10.1371/journal.pone.0118434
Abstract
Ebolaviruses can cause severe hemorrhagic fever that is characterized by rapid viral replication, coagulopathy, inflammation, and high lethality rates. Although there is no clinically proven vaccine or treatment for Ebola virus infection, a virus-like particle (VLP) vaccine is effective in mice, guinea pigs, and non-human primates when given pre-infection. In this work, we report that VLPs protect Ebola virus-infected mice when given 24 hours post-infection. Analysis of cytokine expression in serum revealed a decrease in pro-inflammatory cytokine and chemokine levels in mice given VLPs post-exposure compared to infected, untreated mice. Using knockout mice, we show that VLP-mediated post-exposure protection requires perforin, B cells, macrophages, conventional dendritic cells (cDCs), and either CD4+ or CD8+ T cells. Protection was Ebola virus-specific, as marburgvirus VLPs did not protect Ebola virus-infected mice. Increased antibody production in VLP-treated mice correlated with protection, and macrophages were required for this increased production. However, NK cells, IFN-gamma, and TNF-alpha were not required for post-exposure-mediated protection. These data suggest that a non-replicating Ebola virus vaccine can provide post-exposure protection and that the mechanisms of immune protection in this setting require both increased antibody production and generation of cytotoxic T cells.

Impact of Ten-Valent Pneumococcal Conjugate Vaccination on Invasive Pneumococcal Disease in Finnish Children – A Population-Based Study
Jukka Jokinen, Hanna Rinta-Kokko, Lotta Siira, Arto A. Palmu, Mikko J. Virtanen, Hanna Nohynek, Anni Virolainen-Julkunen, Maija Toropainen, J. Pekka Nuorti
Research Article | published 17 Mar 2015 | PLOS ONE 10.1371/journal.pone.0120290

Research Article
A New Approach to Improving Healthcare Personnel Influenza Immunization Programs: A Randomized Controlled Trial
Larry W. Chambers, Lois Crowe, Po-Po Lam, Donna MacDougall, Shelly McNeil, Virginia Roth,
Kathryn Suh, Catherine Dalzell, Donna Baker, Hilary Ramsay, Sarah DeCoutere, Heather L. Hall, Anne E. McCarthy
Published: March 17, 2015
DOI: 10.1371/journal.pone.0118368
Abstract
Background
Healthcare personnel influenza immunization rates remain sub-optimal. Following multiple studies and expert consultations, the “Successful Influenza Immunization Programs for Healthcare Personnel: A Guide for Program Planners” was produced. This trial assessed the impact of the Guide with facilitation in improving healthcare personnel influenza immunization rates in Canadian healthcare organizations.
Methods
A sample of 26 healthcare organizations across six Canadian provinces (ON, MB, NS, BC, SK, NL) was randomized to Intervention (n=13) or Control groups (n=13). Baseline influenza immunization rates were obtained for 2008–2009; the study groups were followed over two subsequent influenza seasons. The Intervention group received the Guide, facilitation support through workshops for managers and ongoing support. The Control groups conducted programs as usual. The Groups were compared using their reported influenza healthcare personnel influenza immunization rates and scores from a program assessment questionnaire.
Findings
Twenty-six organizations agreed to participate. 35% (9/26) of sites were acute care hospitals, 19% (5/26) continuing care, long-term care organizations or nursing homes, and 46% (12/26) were mixed acute care hospitals and long-term care or regional health authorities. The median rate of influenza immunization among healthcare personnel for the Intervention group was 43%, 44%, and 51% at three points in time respectively, and in the Control group: 62%, 57%, and 55% respectively. No significant differences were observed between the groups at the three points in time. However, there was a 7% increase in the median rates between the Baseline Year and Year Two in the Intervention group, and a 6% decrease in the Control group over the same time period, which was statistically significant (0.071 versus -0.058, p < 0.001).
Interpretation
This pragmatic randomized trial of the Guide with facilitation of its implementation improved healthcare personnel immunization rates, but these rates continued to be sub-optimal and below rates achievable in programs requiring personnel to be immunized.
Trial Registration
ClinicalTrials.gov NCT01207518